Neuroimaging predictors of bariatric surgical outcomes

项目概要/摘要 减肥手术是一个重要的治疗选择病态肥胖患者谁不能减肥通过 饮食和锻炼。尽管进行了干预，20-50%的患者要么未能减掉目标量的体重， 恢复最初失去的体重。预测体重减轻程度的尝试只有适度的 成功和无长期（>2年）可靠性。此外，严重缺乏研究， 预测术后1年或2年后的体重减轻以及体重减轻以外的结局，包括 肥胖人群中常见的合并症。我们在45名患者中的初步数据表明， 用功能性MRI（fMRI）测量的术前神经活动差异可靠地解释了33%的 术后1年体重减轻的差异，以及超过50%的多方面结局指标， 超过了许多其他指标。这些大脑激活预测暗示了与大脑活动密切相关的 一个理论模型，强调消费冲动（一个“现在”的神经回路）与渴望的调节 和自我控制（“后来”电路）。我们的中心假设是，这些神经系统的个体差异 这些途径对维持减肥和实现其他关键健康成果的能力产生强大的影响。 该项目旨在在较长的时间范围内复制和完善这一模型，并评估其预测效用 与体重相关的健康结果。 我们建议复制从我们的功能磁共振成像试验数据预测体重减轻的模型，其次是 探索其对热量摄入、活动水平、肝脏脂肪、血红蛋白A1 c、血脂 血压和空腹血糖在一个新的，独立的队列N=150连续同意， 研究第1-3年的外科袖状胃切除术（SG）患者。我们将跟踪试点队列长达7年 和新的队列进行3年或更长时间的研究，以确定在Aim 1中复制的预测因子是否保持其长期 预测能力，特别是当补充非脑成像变量和使用更大的 纵向数据集。我们将使用成像和非成像数据来开发多变量统计模型 将能量平衡、fMRI和实验室值与目标1中描述的变量相结合，以帮助 独立的预测因素与术后结局的后果。为了帮助分离扫描间变异性， 从真正的手术后，与癫痫相关的大脑变化，我们将招募N=20名肥胖受试者，他们不会 接受减肥手术，并与我们的上述SG受试者单独匹配。最后，就 翻译潜力，我们将评估是否有几个相关的，非功能性磁共振成像认知测试，探测“现在与”。 我们的MRI范例的“后期”功能域可能具有作为临床替代测试的潜力。 帮助预测手术前患者评估期间成功SG结果可能性的实践。 这些研究在理解神经模式在体重中的作用方面都非常重要， 监管和帮助患者实现肥胖人群特定的健康结果。

PROJECT SUMMARY/ABSTRACT Bariatric surgery is an important treatment option for morbidly obese patients who fail to lose weight through diet and exercise. Despite intervention, 20-50% of patients either fail to lose targeted amounts of weight or regain weight that was lost initially. Attempts at predicting the degree of weight loss have had only modest success and none have long term (>2 year) reliability. Moreover, there is a serious absence of research to predict weight loss beyond the 1st or 2nd year post-surgery and for outcomes other than weight loss including comorbidities common in the bariatric population. Our pilot data in 45 patients suggest that individual differences on pre-surgical neural activity measured with functional MRI (fMRI) reliably explains s 33% of the variance in weight loss up to 1 year post surgery, and over 50% of a multifaceted outcome measure, far outperforming many other indicators. These brain activation predictors implicate regions that closely conform to a theoretical model emphasizing both consummatory urges (a “Now” neural circuit) vs. regulation of craving and self-control (a “Later” circuit). Our central hypothesis is that individual differences in these neural pathways exert a powerful effect on the ability to sustain weight loss and achieve other key health outcomes. This project seeks to replicate and refine this model over a longer timeframe and to assess its predictive utility for key weight-related health outcomes. We propose to replicate the model derived from our fMRI pilot data predicting weight loss and secondarily to explore its predictive utility for changes in calorie intake, activity levels, liver fat, hemoglobin A1c, plasma lipids, blood pressure, and fasting glucose in a new, independent cohort of N=150 successively consenting, pre- surgical sleeve gastrectomy (SG) patients in study years 1-3. We will follow the pilot cohort for up to 7 years and the new cohort for 3 or more years to determine if predictors replicated in Aim 1 retain their long-term predictive power, particularly when supplemented with non-brain imaging variables and using a larger longitudinal dataset. We will use imaging and non-imaging data to develop multivariate statistical models incorporating energy balance, fMRI, and laboratory values with the variables described in Aim 1 to help to separate predictors vs. consequences of post-surgical outcomes. To help separate scan-to-scan variability from true post-surgical, trajectory-related brain changes, we will enroll N=20 obese subjects who will not undergo bariatric surgery, and are individually matched with our above SG subjects. Finally, in terms of translational potential, we will evaluate whether several related, non-fMRI cognitive tests that probe "Now vs. Later" functional domains to our MRI paradigms might have the potential to act as surrogate tests in clinical practice that help predict the likelihood of successful SG outcome during pre-surgical patient assessment. These studies are highly significant both in terms of understanding the role of neural patterns in weight regulation and in helping patients achieve bariatric population-specific health outcomes.